Appendix I Description of CATH Domain Structure Database

structures deposited in the Protein Data Bank (PDB, [2]). There are five major classification levels in the CATH hierarchy. The top C level separates domains into different Classes based on the type of secondary structure within the domain, principally mainly-α helices, mainly β-strands or a mixture of the two, α-β. The A level divides the classes into different Architectures, which describes the shape of a protein, given by the secondary structure orientations in 3D, regardless of their connectivity e.g. the protein resembles a barrel or a sandwich. The T level divides these architectures into their distinct Topologies (folds). The topology of a protein details the specific connectivity amongst the secondary structures. At the Homology level, folds are further separated into superfamilies that have a high structural and sequence or functional similarity, indicating evolution from a common ancestor. The S level divides the homologous structures into Sequence families. Members of the individual S families have ≥35 % sequence identity to at least one other relative and have very similar structures and functions